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Xie J.-H.,Guangzhou University of Chinese Medicine | Chen Y.-L.,Guangzhou University of Chinese Medicine | Wu Q.-H.,Guangzhou University of Chinese Medicine | Wu J.,Shandong CoIlege of Traditional Chinese Medicine | And 8 more authors.
BMC Complementary and Alternative Medicine | Year: 2013

Background: A traditional Chinese Medicine (TCM) formula, HZJW, has been applied in clinics in China for gastrointestinal disorders. However, the therapeutic mechanism underlying its efficacy and safety remained to be defined. The present investigation was undertaken to evaluate the formula HZJW for its gastroprotective potential, possible effect on Helicobacter pylori along with safety to justify its anti-ulcer action and safe clinical application. Methods: The gastroduodenal cytoprotective potential was evaluated in rodent experimental models (HCl/Ethanol and NSAID-induced ulcer protocols). The anti-H. pylori property was assessed by agar dilution assay in vitro and analysis in vivo including rapid urease test, immunogold test and histopathology. For toxicity assessment, acute toxicity study was performed according to fixed dose procedure with a single oral administration of HZJW to mice. In the oral chronic toxicity, rats (80 males, 80 females) were administrated HZJW orally in 0, 1000, 2500, or 5000 mg/kg/day doses for 26 weeks (n = 40/group of each sex). Clinical signs, mortality, body weights, feed consumption, ophthalmology, hematology, serum biochemistry, gross findings, organ weights and histopathology were examined at the end of the 13- and 26-week dosing period, as well as after the 4-week recovery period.Results: In the HCl/Ethanol-induced ulcer model, it was observed that oral administration with HZJW (260, 520 and 1040 mg/kg) and ranitidine (250 mg/kg) significantly reduced the ulcerative lesion index (116.70 ± 36.4, 102.20 ± 18.20, 84.10 ± 12.1 and 73.70 ± 16.70) in a dose-dependent manner, respectively, with respect to control group (134.10 ± 31.69). Significant inhibition was also observed in ulcerative index from aspirin-induced ulcer model, with decreases of 35.40 ± 5.93, 31.30 ± 8.08, 26.80 ± 8.27and 20.40 ± 6.93 for the groups treated with HZJW and ranitidine, in parallel to controls (41.60 ± 10.80). On the other hand, treatment with HZJW efficaciously eradicated H. pylori in infected mice in rapid urease test (RUT) and immunogold antibody assay, as further confirmed by reduction of H. pylori presence in histopathological analysis. In the in vitro assay, MICs for HZJW and amoxicillin (positive control) were 125 and 0.12 μg/mL respectively. The LD50 of HZJW was over 18.0 g/kg for mice. No drug-induced abnormalities were found as clinical signs, body weight, food consumption, hematology, blood biochemistry, ophthalmology and histopathology results across three doses. No target organ was identified. The No Observed Adverse Effect Level (NOAEL) of HZJW was determined to be 5,000 mg/kg/day for both sexes, a dose that was equivalent to 50 times of human dose.Conclusions: These results suggested the efficacy and safety of HZJW in healing peptic ulcer and combating H. pylori, which corroborated their conventional indications and contributed to their antiulcer pharmacological validation, lending more credence to its clinical application for the traditional treatment of stomach complaints symptomatic of peptic ulcer disease (PUD). HZJW might have the potential for further development as a safe and effective alternative/complementary to conventional medication in treating gastrointestinal (GI) disorders. © 2013 Xie et al.; licensee BioMed Central Ltd. Source


Tong M.C.F.,Chinese University of Hong Kong | Gao H.,Chinese University of Hong Kong | Gao H.,Shenzhen ENT Institute | Lin J.S.C.,Chinese University of Hong Kong | And 3 more authors.
Journal of Otolaryngology - Head and Neck Surgery | Year: 2012

Objective: To evaluate the feasibility of a one-stop assessment of patients complaining of globus sensation with transnasal esophagoscopy (TNE) and functional endoscopic evaluation of swallowing (FEES). Design: Prospective, nonrandomized, experimental investigation. Setting: Tertiary referral centre. Methods: Sixty-three consecutive patients complaining of a lump in the throat were evaluated by this combined approach. Main Outcome Measures: The safety and feasibility of performing a one-stop TNE plus FEES were explored by subjective measurement of the patients' tolerance and satisfaction and comments from surgeons. The possible therapeutic effects were also assessed 2 months after the procedure. Results: All 63 patients completed the TNE and FEES without any complications. The average duration of the examination was 6.27 ± 2.52 (95% CI 5.63-6.91) minutes. The findings included arytenoid cyst, epiglottic cyst, vocal cord nodules, vocal cord palsy, esophageal reflux, and foveolar gland hyperplasia. Two patients (3.2%) demonstrated some degree of fluid penetration or aspiration. Nine specialists all scored highly on a visual analogue scale on the manipulation, visualization, and satisfaction of the TNE procedure (median = 8 of 10). Patients also rated a low pain score (median = 1 of 10) and a high satisfaction score (median = 9 of 10). Conclusion: The combined technique of TNE and FEES can be used safely as a one-stop examination tool for patients with globus pharyngeus symptoms. © 2012 The Canadian Society of Otolaryngology-Head & Neck Surgery. Source


Wang S.,Comprehensive Care | Deng Z.,Comprehensive Care | Deng Z.,Shenzhen ENT Institute | Seneviratne C.J.,National University of Singapore | And 5 more authors.
Innate Immunity | Year: 2015

Enterococcus faecalis is considered a major bacterial pathogen implicated in endodontic infections and contributes considerably to periapical periodontitis. This study aimed to investigate the potential mechanisms by which E. faecalis accounts for the bone destruction in periapical periodontitis in vitro. Osteoclast precursor RAW264.7 cells were treated with E. faecalis ATCC 29212 and a wild strain of E. faecalis derived clinically from an infected root canal. The results showed that, to some extent, E. faecalis induced the RAW264.7 cells to form tartrate-resistant acid phosphatase (TRAP)-positive multinucleated osteoclast-like cells. This pathogen markedly stimulated RAW264.7 cells to express semaphorin 4D (Sema4D), which inhibits bone formation. Once RAW264.7 cells were primed by low-dose receptor activator of nuclear factor-kappa B ligand (RANKL), E. faecalis could significantly increase the production of TRAP-positive multinucleated cells and up-regulate the expression of osteoclast-specific markers, including NFATc1, TRAP and cathepsin K. Both p38 and ERK1/2 MAPK signaling pathways were activated by E. faecalis in RANKL-primed RAW264.7 cells, and meanwhile the expression of Sema4D was highly increased. In conclusion, E. faecalis may greatly contribute to the bone resorption in periapical periodontitis by promoting RANKL-dependent osteoclastogenesis and expression of Sema4D through activation of p38 and ERK1/2 MAPK signaling pathways. © SAGE Publications. Source


Qiu S.,Shenzhen ENT Institute | Du Y.,Hebei Medical University | Duan X.,Shenzhen ENT Institute | Geng X.,Shenzhen ENT Institute | And 3 more authors.
Journal of Clinical Immunology | Year: 2012

Background The pathogenesis of allergic diseases is to be further understood. Recent studies indicate that B cells are involved in the immune regulation. The present study aimed to investigate the role of B cells in the initiation of skewed T helper (Th)2 polarization. Methods The surgically removed nasal mucosal specimens from 24 patients with allergic rhinitis (AR) and 22 patients with non-AR (nAR) were collected. B cells isolated from the AR nasal mucosa were characterized. The effect of B cells on inducing naïve CD4+ T cells to differentiate into Th2 cells was evaluated with a cell culture model. Results Abundant B cells were detected in the nasal mucosa of patients with AR, which also expressed high levels of T cell immunoglobulin mucin domain (TIM)4 and costimulatory molecules. High levels of Staphylococcal enterotoxin B (SEB) were detected in the AR nasal mucosa. Expression of TIM4 could be induced in naïve B cells in the presence of SEB in culture. TIM4+ B cells could induce naïve CD4+ T cells to differentiate into Th2 cells. Conclusions TIM4+ B cells from AR nasal mucosa can induce skewed Th2 polarization. It may be a potential therapeutic target in the treatment of AR. Capsule summary B cells plays an important role in the initiation of Th2 polarization. © Springer Science+Business Media, LLC 2012. Source


Qiu S.,Shenzhen ENT Institute | Qiu S.,ENT Hospital | Du Y.,McMaster University | Du Y.,Hebei Medical University | And 6 more authors.
North American Journal of Medical Sciences | Year: 2011

Background: The prevalence of chronic rhinitis is increasing rapidly; its pathogenesis is to be further understood; immune inflammation is one of the possible causative factors. Antigen specific CD8+ T cells play a critical role in the induction of chronic inflammation. Aims: This study aimed to investigate the role of antigen specific CD8+ T cells in the pathogenesis of chronic atypical allergic rhinitis. Material and Methods: Nasal mucosal epithelial surface scratching samples were obtained from patients with chronic obstruction atypical allergic rhinitis. Exosomes were purified from the scratching samples and examined by immune gold electron microscopy. The effect of exosomes on modulating dendritic cell's properties, the effect of exosome-pulsed dendritic cells on naïve T cell differentiation and the antigen specific CD8+ T cell activation were observed by cell culture models. Results: Exosomes purified from patients with chronic atypical allergic rhinitis carried microbial products, Staphylococcal enterotoxin B (SEB), and airborne antigen, Derp1. Dendritic cells pulsed by SEB/Derp1-carrying exosomes showed high levels of CD80, CD86 and the major histocompatibility class I (MHCI). Exosome-pulsed dendritic cells could induce the naïve CD3+ T cells to differentiate into CD8+ T cells. Upon the exposure to a specific antigen, the CD8+ T cells released granzyme B and perforin; more than 30% antigen specific CD8+ T cells proliferated. Conclusions: Antigen specific CD8+ T cells play an important role in the pathogenesis of chronic obstruction atypical allergic rhinitis. Source

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